Postacute ischemia vascular endothelial growth factor transfer by transferrin-targeted liposomes attenuates ischemic brain injury after experimental stroke in rats.
Abstract
Our objective was to achieve the enhanced delivery of vascular endothelial growth factor (VEGF) to ischemically disordered brain through transferrin-coupled liposomes (Tf-PLs) via intravenous administration, and to observe the effect of Tf-VEGF-PLs on ischemic brain neuroprotection and angiogenesis. Cerebral VEGF overexpression was achieved with Tf-PLs by intravenous injection 48 hr after an acute stroke. β-Galactosidase expression was monitored; saline was injected as a control. The success of postischemic gene transduction was confirmed by β-galactosidase staining and by increased VEGF mRNA and protein in ischemic brain. Vascular density, neurological recovery, and ischemic area calculation were performed to evaluate the effect of Tf-VEGF-PLs. The positive expression of β-galactosidase indirectly indicated that VEGF was successfully delivered into brain by Tf-VEGF-PLs. VEGF mRNA in the Tf-VEGF-PL group 24 hr after injection was significantly higher than in the control group (p < 0.05). Western blot analysis showed that postischemic Tf-VEGF-PLs resulted in increased VEGF protein levels compared with VEGF-PLs and saline-administered rats (p < 0.05) 48 hr after administration. At 21 days after drug injection, we observed a significant decrease in infarct volume and better neurological function in the Tf-VEGF-PL-treated group, compared with the VEGF-PL group. FITC-dextran marking showed increased vascular density in the penumbra of Tf-VEGF-PL-treated hemispheres (245,873.9, number of microvessels per field) compared with that in VEGF-PL-treated hemispheres (139,801.3) or saline-treated hemispheres (102,175.5) (p < 0.05). The remainder of the cerebral blood flow after ischemia in the Tf-VEGF-PL group was significantly more than in the control groups (0.35 vs. 0.29, 0.21; p < 0.05). We conclude that the VEGF gene can be delivered noninvasively into the brain by Tf-VEGF-PLs. Postischemic treatment with Tf-VEGF-PLs effectively promoted neuroprotection and vascular regeneration in the chronic stage of cerebral infarction.
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Encapsulation of VEGF-encoding plasmids in Tf-LPs achieves enhanced delivery of VEGF to the ischemic brain.
“Zhao et al. (2010) achieved enhanced delivery of VEGF to the ischemic brain by encapsulated VEGF-encoding plasmids in Tf-LPs.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Zhao et al., 2010
Rats treated with Tf-LPs exhibit increased levels of VEGF mRNA and protein in the ischemic brain compared with rats treated with unmodified liposomes or saline.
“It was found that the rats treated with Tf-LPs exhibited increased levels of VEGF mRNA and protein in the ischemic brain, compared with the rats treated with unmodified liposomes or saline.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Zhao et al., 2010
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Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs
Naqvi, S., Panghal, A., & Flora, S. J. S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00494 · Cited by 305 · see citing works
“Zhao et al. (2010) achieved enhanced delivery of VEGF to the ischemic brain by encapsulated VEGF-encoding plasmids in Tf-LPs.”
BackgroundTherapeutics, imaging and toxicity of nanomaterials in the central nervous system.
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- Authors
- Zhao, H., Bao, X.-J., Wang, R.-Z., Li, G.-L., Gao, J., Ma, S.-H., Wei, J.-J., Feng, M., Zhao, Y.-J., Ma, W.-B., Yang, Y., Li, Y.-N., & Kong, Y.-G.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2010-12-02
- Volume
- 22
- Issue
- 2
- Pages
- 207-215
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W2052965918
- Cited by
- 73
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Peking University
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- vascular endothelial growth factor, gene transfer, ischemic stroke, neuroprotection, angiogenesis, cerebral ischemia, infarct size, neurological recovery, vessel density, cerebral blood flow, liposomal drug delivery, penumbra, rats, lacZ reporter, VEGF mRNA
- MeSH terms
- Animals, beta-Galactosidase, Brain, Brain Ischemia, Dextrans, Disease Models, Animal, Injections, Intravenous, Liposomes, Male, Transferrin, Genetic Therapy, Fluorescein-5-isothiocyanate, Rats, Sprague-Dawley, Neuroprotective Agents, Stroke, Vascular Endothelial Growth Factor A, Rats
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